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Ok...............here is something interesting. For those who know and followed my, Robin and Wesley's highly technical discussions in 2004 and 2005, you all will probably understand this. If not, you might not understand.

For once, though, I'm not going to go into overdrive with my usual explanations, etc.

I just know that Robin may find this particularly interesting. Especially when he sees the word "microglia".

Also, the minocycline folks may find the following interesting.

What do you think, Robin?

Deb

P.S. Needless to say, the NMSS and others are also aware. I hate to tell them "I told you so", but.................well, wait a minute, no I don't. I LOVE to tell them "I told you so"! hehehe........

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J Neuroimmunol. 2005 Dec 28; [Epub ahead of print] Links

The involvement of norepinephrine and microglia in hypothalamic and splenic IL-1beta responses to stress.

Blandino P Jr, Barnum CJ, Deak T.

Behavioral Neuroscience Program, Department of Psychology, State University of New York at Binghamton, Binghamton, NY 13902-6000, USA.The noradrenergic system plays an integral role in the stress response and modulates expression of proinflammatory cytokines. Recent work from our laboratory and others has shown that certain stressors increase the expression of the proinflammatory cytokine interleukin-1beta (IL-1beta) in the hypothalamus and spleen. One goal of the following studies was to assess the role of norepinephrine in stress-elicited increases in IL-1beta. To do this, adult male Sprague-Dawley rats were injected with propranolol (20 mg/kg i.p.) or desipramine (20 mg/kg s.c.) and exposed to 80 inescapable footshocks (2.0 mA, 90 s variable ITI, 5 s each). We found that propranolol blocked the IL-1beta response to footshock in both the hypothalamus and the spleen, while the noradrenergic reuptake inhibitor desipramine significantly augmented the footshock-induced IL-1beta response in both of these sites.Our second goal was to determine whether these effects would also be blocked by administration of a putative microglial inhibitor (minocycline). Minocycline (40 mg/kg i.p.) completely reversed the footshock-induced increase in hypothalamic IL-1beta but had no effect on the IL-1beta response in the spleen. Moreover, lack of an effect of minocycline on conditioned fear responding suggests that the effect of this drug cannot be explained by nonspecific sedative properties produced by the drug. Together, these data suggest that NE powerfully modulates the hypothalamic and splenic IL-1beta response to stress, and that microglia may be a primary cellular source of central IL-1beta in response to footshock.

PMID: 16386803 [PubMed - as supplied by publisher]

Eur Neuropsychopharmacol. 2005 Dec 30; [Epub ahead of print] Links

Antidepressants suppress production of the Th(1) cytokine interferon-gamma, independent of monoamine transporter blockade.

Diamond M, Kelly JP, Connor TJ.

Department of Pharmacology, National University of Ireland, Galway, Ireland.

In this study, antidepressants with selectivity for the noradrenaline transporter (reboxetine and desipramine), or the serotonin transporter (fluoxetine and clomipramine) were examined in terms of their ability to promote an anti-inflammatory cytokine phenotype in human blood. In addition, we examined the ability of trimipramine; a tricyclic antidepressant that is devoid of monoamine reuptake inhibitory properties on cytokine production. Lipopolysaccharide (LPS) was used to stimulate monocyte-derived pro-inflammatory (IL-1beta, TNF-alpha, IL-12) and anti-inflammatory (IL-10) cytokines, whilst concanavalin A (Con A) was used to stimulate T-cell (Th(1): IFN-gamma and Th(2/3): IL-10) cytokines. All of the antidepressants suppressed IFN-gamma production in the 10-50 muM concentration range, irrespective of their preference for serotonin or noradrenaline transporters. This suppression of IFN-gamma production was paralleled by reduced T-cell proliferation, therefore we suggest that the ability of antidepressants to suppress IFN-gamma production may be related to their anti-proliferative properties. The fact that trimipramine also suppressed IFN-gamma production and T-cell proliferation indicates that these immunomodulatory actions of antidepressants are most likely unrelated to inhibition of monoamine reuptake. Interestingly, exposure to a lower concentration (1 muM) of the antidepressants tended to increase T-cell-derived IL-10 production, with significant effects elicited by the noradrenaline reuptake inhibitors reboxetine and desipramine. In contrast to the robust actions of antidepressants on T-cell derived cytokine production, they failed to induce any consistent change in LPS-induced monocyte cytokine production. Overall, our results indicate that IFN-gamma producing T-cells (Th(1) cells) are the major target for the immunomodulatory actions of antidepressants, and provide evidence questioning the relationship between the monoaminergic reuptake properties of antidepressants and their immunomodulatory effects. The potential clinical significance of the anti-inflammatory actions of antidepressants is discussed.

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DOSAGE is of primary importance. If the dose of desipramine is too high, how it effects IL1B, etc. changes. A low dose of desipramine attenuates IL1B (as previous research I have posted indicates time and time again.)

Chronic use is also of importance.

Oh, and in addition, TNFa is also decreased. (Again, as shown in previous studies.)

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